Rubedo Life Sciences reported preliminary Phase 1 results for topical RLS-1496 from a single-center, ascending-dose, randomized, double-blind, vehicle-controlled trial conducted in the European Union. The study met its primary endpoint and showed early signs of efficacy, with no serious adverse events and no discontinuations during the four-week study.
In plaque psoriasis patients, investigators observed a clear dose response across 0.1%, 0.5% and 1.0% cohorts, dose-related target engagement of RLS-1496 with GPX4, reductions in senescent cells in mid- and high-dose cohorts, and an average 20 percent reduction in epidermal thickness on histology; a statistically significant relationship was seen between target engagement and improvement in clinical psoriasis severity, according to the company.
In atopic dermatitis subjects, the company reports higher target engagement and substantial clinical improvement, with 25 percent of treated subjects achieving a four-point or greater improvement on the pruritus numeric rating scale, compared with none in the vehicle group. Early photo-aging analyses showed dose-dependent target engagement in non-lesional photo-aged skin, increased collagen gene and protein expression, and reduced SASP and inflammatory biomarker levels in keratinocytes.
A Phase 1b/2a actinic keratosis study is underway in the United States with completion expected later this year, and Rubedo expects data from roughly 70 subjects across its trials. RLS-1496 is a first-in-class GPX4 modulator being developed for topical and oral use; the company claims that the mechanism selectively targets pathological senescent cells and may clear them, restoring tissue homeostasis.
